title: Safety and efficacy of metformin for therapy-induced hyperglycemia in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  Hyperglycemia during corticosteroid and asparaginase therapy for acute lymphoblastic leukemia is a significant side effect that is usually treated with insulin. Metformin is an oral antidiabetic biguanide that may cause metabolic acidosis and liver enzyme abnormalities of possible concern in patients receiving chemotherapy.
  
  
  METHODS
  We reviewed patients with acute lymphoblastic leukemia treated with corticosteroids and asparaginase who received metformin for control of hyperglycemia.
  
  
  RESULTS
  Seventeen patients received metformin, including 4 who received insulin before starting metformin therapy. Twelve were treated during initial induction therapy and 5 during relapse reinduction. Corticosteroids included dexamethasone in 11, prednisone in 5, and megesterol in 1. Fifteen received pegasparaginase.Patients were treated with metformin for a median of 6 days (range, 2 to 46 d). Metformin was started at a median glucose level of 286 mg/dL (range, 112 to 499 mg/mL). The glucose level was controlled with metformin alone in 12 patients without the need for insulin. Four patients received insulin before or concomitantly with metformin. In 1 patient, metformin failed to control the glucose level, and insulin was administered.No significant toxicity from metformin was seen. Two patients had an elevated anion gap and creatinine level because of extreme hyperglycemia. One patient had mild elevation in total bilirubin and 5 patients had mild elevation in serum alanine aminotransferase levels. There were no episodes of hypoglycemia.
  
  
  CONCLUSIONS
  Metformin is safe and effective for therapy-induced hyperglycemia. Initially, insulin may be required for significant hyperglycemia or metabolic abnormalities. We are unaware of any prior studies using metformin in this population.
authors.affiliation: Departments of *Pediatric Hematology/Oncology †Pediatric Endocrinology, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN.
authors.forename: Bruce
authors.initials: B
authors.lastname: Bostrom
authors.forename: Priya
authors.initials: P
authors.lastname: Uppal
authors.forename: Julie
authors.initials: J
authors.lastname: Chu
authors.forename: Yoav
authors.initials: Y
authors.lastname: Messinger
authors.forename: Laura
authors.initials: L
authors.lastname: Gandrud
authors.forename: Robert
authors.initials: R
authors.lastname: McEvoy
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced* / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin